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World J Gastroenterol. Dec 21, 2014; 20(47): 17830-17838
Published online Dec 21, 2014. doi: 10.3748/wjg.v20.i47.17830
Dendritic cells in hepatitis C virus infection: Key players in the IFNL3-genotype response
Kate S O’Connor, Jacob George, David Booth, Golo Ahlenstiel
Kate S O’Connor, David Booth, Institute for Immunology and Allergy Research, Westmead Millennium Institute, University of Sydney, Sydney, NSW 2145, Australia
Jacob George, Golo Ahlenstiel, Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, NSW 2145, Australia
Author contributions: All authors significantly contributed to the writing and editing of the manuscript.
Supported by Robert W Storr Bequest to the Sydney Medical Foundation Work program and a National Health and Medical Research Council of Australia (NHMRC) Program Grant, APP1053206 (to George J and Ahlenstiel G); research grants from the NHMRC (partly), APP1006759 and ARC Linkage Grant, LP0990067; the Hunt Family Senior Research Fellowship (to Booth D)
Correspondence to: Golo Ahlenstiel, Associate Professor, Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Hawkesbury Road, Westmead, Sydney, NSW 2145, Australia. golo.ahlenstiel@sydney.edu.au
Telephone: +61-2-98457986 Fax: +61-2-98455118
Received: June 12, 2014
Revised: July 14, 2014
Accepted: July 24, 2014
Published online: December 21, 2014
Abstract

Recently, single nucleotide polymorphisms, in the vicinity of the interferon lambda 3 (IFNL3) gene have been identified as the strongest predictor of spontaneous and treatment induced clearance of hepatitis C virus (HCV) infection. Since then, increasing evidence has implicated the innate immune response in mediating the IFNL3 genotype effect. Dendritic cells (DCs) are key to the host immune response in HCV infection and their vital role in the IFNL3 genotype effect is emerging. Reports have identified subclasses of DCs, particularly myeloid DC2s and potentially plasmacytoid DCs as the major producers of IFNL3 in the setting of HCV infection. Given the complexities of dendritic cell biology and the conflicting current available data, this review aims to summarize what is currently known regarding the role of dendritic cells in HCV infection and to place it into context of what is know about lambda interferons and dendritic cells in general.

Keywords: Hepatitis C virus, Interferon lambda 3, Dendritic cells, Plasmacytoid dendritic cells, Myeloid dendritic cells, Innate immunity

Core tip: Increasing evidence implicates the innate immune response in mediating the interferon lambda 3 (IFNL3) genotype effect in hepatitis C virus (HCV) infection. Dendritic cells (DCs) are essential players in the host immune response to HCV infection, especially with respect to the IFNL3 genotype effect. Subsets of DCs, myeloid DC2s and potentially plasmacytoid DCs, appear to particularly important in orchestrating the IFNL3 genotype effect.